A decisive bridge between innate immunity and the pathognomonic morphological characteristics of type 1 diabetes demonstrated by instillation of heat-inactivated bacteria in the pancreatic duct of rats

通过在大鼠胰管中灌注热灭活细菌证明了先天免疫与 1 型糖尿病的病理形态特征之间的决定性桥梁

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作者:Tegehall Angie, Ingvast Sofie, Melhus Åsa, Skog Oskar, Korsgren Olle

Aims

Periductal inflammation and accumulation of granulocytes and monocytes in the periislet area and in the exocrine pancreas is observed within hours after instillation of heat-inactivated bacteria in the ductal compartment of the pancreas in healthy rats. The present investigation was undertaken to study how the acute inflammation developed over time.

Conclusions

The results presented unravel a previously unknown interplay between innate and acquired immunity in the formation of immunopathological events indistinguishable from those described in humans with recent onset T1D.

Methods

Immunohistochemical evaluation of the immune response triggered by instillation of heat-inactivated bacteria in the ductal compartment in rats.

Results

After three weeks, the triggered inflammation had vanished and pancreases showed normal morphology. However, a distinct accumulation of both CD4+ and CD8+ T cells within and adjacent to affected islets was found in one-third of the rats instilled with heat-inactivated E. faecalis, mimicking the insulitis seen at onset of human T1D. As in T1D, this insulitis affected a minority of islets and only certain lobes of the pancreases. Notably, a fraction of the T cells expressed the CD103 antigen, mirroring the recently reported presence of tissue resident memory T cells in the insulitis in humans with recent onset T1D. Conclusions: The results presented unravel a previously unknown interplay between innate and acquired immunity in the formation of immunopathological events indistinguishable from those described in humans with recent onset T1D.

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